Vγ9Vδ2 T cell proliferation agent, method for producing activated Vγ9Vδ2 T cells, and uses thereof

Abstract

A Vγ9Vδ2 T cell proliferation agent includes at least a bisphosphonate, interleukin 2, and interleukin 18. Since IL-18 has properties that improve cell viability by inhibiting cell death, IL-18 is presumably capable of acting as a cofactor for the bisphosphonate so as to significantly increase the effect of Vγ9Vδ2 T cell proliferation by the bisphosphonate and the IL-2. This allows providing a Vγ9Vδ2 T cell proliferation agent capable of growing Vγ9Vδ2 T cells with a proliferated efficiency significantly high compared to conventional methods so that the proliferated Vγ9Vδ2 T cells have a high antitumor activity and high cytokine productivity.

Description

[0001]This Nonprovisional application claims priority under 35 U.S.C. §119(a) on Patent Application No. 180749 / 2008 filed in Japan on Jul. 10, 2008, the entire contents of which are hereby incorporated by reference.FIELD OF THE INVENTION[0002]The present invention relates to a Vγ9Vδ2 T cell proliferation agent, a method for producing activated Vγ9Vδ2 T cells, and use of the proliferation agent and the activated Vγ9Vδ2 T cells. More particularly, the present invention relates to (i) a Vγ9Vδ2 T cell proliferation agent containing at least a bisphosphonate, interleukin 2, and interleukin 18, (ii) a method for producing activated Vγ9Vδ2 T cells, the method comprising stimulating Vγ9Vδ2 T cells by using at least a bisphosphonate, interleukin 2, and interleukin 18, (iii) the activated Vγ9Vδ2 T cells and a medicine containing the same, and (iv) a Vγ9Vδ2 T cell proliferation kit.[0003]The Vγ9Vδ2 T cell proliferation agent of the present invention contains at least bisphosphonate, interleuki...

AI Technical Summary

Benefits of technology

[0011]IL-18 is a cytokine discovered by Okamura et al. in 1995 as an IFN-γ inducing factor (Okamura et al., Nature 378:88-91, 1995). It has been revealed in recent years that IL-18 has various biological actions. The inventors of the present invention have reported that IL-18 significantly increases the population sizes of activated CD8-positive T lymphocytes and NK cells by inhibiting apoptosis of such cells, and that the activated CD8-positive T cells strongly express an IL-18 receptor β chain and stimulation by IL-18 enhances the effect of factors such as PI3K / Akt and Bc12, which augment cell viability (Li Wen et al., J. Leukocyte Biol., 82, 142-151, 2007).

[0012]As described above, IL-18 has properties that improve cell viability by inhibiting cell death. Therefore, IL-18 is presumably capable of acting as a cofactor for a bisphosphonate so as to significantly improve the effect of growing Vγ9Vδ2 T cells by a bisphosphonate and IL-2. Thus, the above arrangement allows highly efficient growth of Vγ9Vδ2 T cells.

[0013]A method for producing an activated Vγ9Vδ2 T cell of the present invention includes stimulating a Vγ9Vδ2 T cell by at least a bisphosphonate, interleukin 2, and interleukin 18. As described above, the combinational use of a bisphosphonate, IL-2, and IL-18 allows efficient growth of Vγ9Vδ2 T cells. Furthermore, as shown in an example described below, the Vγ9Vδ2 T cells thus proliferated have a high antitumor activity and high cytokine productivity. Thus, the above arrangement allows highly efficient production of Vγ9Vδ2 T cells having superior bioactivities.

[0015]A Vγ9Vδ2 T cell proliferation kit of the present invention includes at least a Vγ9Vδ2 T cell, a bisphosphonate, interleukin 2, and interleukin 18. According to the above arrangement, materials minimally required for the growth of Vγ9Vδ2 T cells are included as a prepared set. This allows the proliferation of Vγ9Vδ2 T cells to be carried out in a simple and easy manner.

[0016]As described above, the Vγ9Vδ2 T cell proliferation agent of the present invention, which includes at least a bisphosphonate, interleukin 2, and interleukin 18, is capable of highly efficiently growing Vγ9Vδ2 T cells, which have conventionally been unable to be proliferated sufficiently. Furthermore, the Vγ9Vδ2 T cell proliferation agent is also capable of providing the Vγ9Vδ2 T cells thus proliferated with a superior antitumor action and superior cytokine productivity.

Problems solved by technology

However, a limited quantity of Vγ9Vδ2 T cells present in human peripheral blood makes it difficult to obtain a sufficient amount of Vγ9Vδ2 T cells for use in immunotherapy.

However, such conventional arts have a problem in that Vγ9Vδ2 T cells cannot be proliferated sufficiently.

This necessitates collecting a large amount of peripheral blood from the patient, thereby giving the patient much pain and burden.

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